Publications by authors named "Xiao-Li Li"

361 Publications

Silk fibroin/chitosan/TGF-β1-loaded microsphere scaffolds for cartilage reparation.

Biomed Mater Eng 2021 Jul 7. Epub 2021 Jul 7.

Key Laboratory of Biomedical Materials and Implant Devices, Research Institute of Tsinghua University in Shenzhen, Shenzhen, China.

Background: Transforming growth factor-β1 (TGF-β1) plays an important role in chondrocyte growth and the synthesis of extracellular matrix (ECM). Due to the rapid metabolism, controlled release systems for TGF-β1 have attracted increasing interest recently.

Objective: In this study, a silk fibroin (SF)/chitosan (CS) scaffold incorporated with TGF-β1-loaded microspheres (MSs) was created for cartilage reparation.

Method: The optimal proportion of the SF/CS composite scaffold was determined by evaluating their micromorphology and the proliferation rate of fibroblasts on the surface. Then, SF/CS/TGF-β1-loaded MS scaffolds were prepared by the adsorption method. TGF-β1 release capacity, degradation patterns, cytocompatibility and in vivo implantation were evaluted.

Results: The SF/CS/TGF-β1-loaded MS scaffold showed good TGF-β1 release over more than 16 days, which could sequentially stimulate chondrocyte synthetic activity. In vitro cell proliferation experiments showed the SF/CS/TGF-β1-loaded MS scaffold could promote chondrocytes adhesion, growth, proliferation and maintained the cellular morphology. An in vivo study demonstrated that a low inflammatory response was observed in rats and that the materials exhibited good biocompatibility.

Conclusion: the results indicated that our SF/CS/TGF-β1-loaded MS scaffold constitute a promising therapeutic option for cartilage reparation.
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http://dx.doi.org/10.3233/BME-201178DOI Listing
July 2021

A CT-based radiomics nomogram for differentiation of squamous cell carcinoma and non-Hodgkin's lymphoma of the palatine tonsil.

Eur Radiol 2021 Jul 8. Epub 2021 Jul 8.

Department of Radiology, The Affiliated Hospital of Qingdao University, NO. 16, Jiangsu Road, Qingdao, 266000, China.

Objectives: Accurate preoperative differentiation between squamous cell carcinoma (SCC) and non-Hodgkin's lymphoma (NHL) in the palatine tonsil is crucial because of their different treatment. This study aimed to construct and validate a contrast-enhanced CT (CECT)-based radiomics nomogram for preoperative differentiation of SCC and NHL in the palatine tonsil.

Methods: This study enrolled 135 patients with a pathological diagnosis of SCC or NHL from two clinical centers, who were divided into training (n = 94; SCC = 50, NHL = 44) and external validation sets (n = 41; SCC = 22, NHL = 19). A radiomics signature was constructed from radiomics features extracted from routine CECT images and a radiomics score (Rad-score) was calculated. A clinical model was established using demographic features and CT findings. The independent clinical factors and Rad-score were combined to construct a radiomics nomogram. Performance of the clinical model, radiomics signature, and nomogram was assessed using receiver operating characteristics analysis and decision curve analysis.

Results: Eleven features were finally selected to construct the radiomics signature. The radiomics nomogram incorporating gender, mean CECT value, and radiomics signature showed better predictive value for differentiating SCC from NHL than the clinical model for training (AUC, 0.919 vs. 0.801, p = 0.004) and validation (AUC, 0.876 vs. 0.703, p = 0.029) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model.

Conclusions: A CECT-based radiomics nomogram was constructed incorporating gender, mean CECT value, and radiomics signature. This nomogram showed favorable predictive efficacy for differentiating SCC from NHL in the palatine tonsil, and might be useful for clinical decision-making.

Key Points: • Differential diagnosis between SCC and NHL in the palatine tonsil is difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, gender, and mean contrast-enhanced CT value facilitates differentiation of SCC from NHL with improved diagnostic efficacy.
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http://dx.doi.org/10.1007/s00330-021-08153-9DOI Listing
July 2021

Comparison of the prognostic value of SYNTAX score and clinical SYNTAX score on outcomes of Chinese patients underwent percutaneous coronary intervention.

BMC Cardiovasc Disord 2021 Jul 7;21(1):334. Epub 2021 Jul 7.

Department of Cardiology, Chongqing General Hospital, University of Chinese Academy of Sciences, No. 108, Xingguang Road, Liangjiang New District, Chongqing, China.

Background: Previous studies have validated the capability of SYNTAX score (SS) and clinical SYNTAX score (CSS) in the prediction of clinical outcomes in patients who have undergone PCI; however, studies on comparison of these two scoring systems in Chinese population have been sparse.

Methods: To study the ability of SS and CSS in prediction of clinical outcomes of Chinese patients underwent percutaneous coronary intervention (PCI). We retrospectively calculated SS and CSS for 547 Chinese patients from a single center who underwent PCI. Patients were stratified into tertiles according to their SS and CSS. We compared the 2-year clinical outcomes in these patients stratified separately by SS and CSS tertiles.

Results: The incidence of major adverse cardiac and cerebro-vascular events (MACCE) was the highest in patients with SS (13.5%), comparing to 6.8% in SS and 0% in SS (p < 0.0001). The Cox multivariable analysis showed that the SS and CSS were both strong independent predictors for MACCE [1.100 (1.069-1.133), 1.017 (1.010-1.025), both p < 0.0001]. The receiver operating characteristic (ROC) curves showed the areas-under-the-curves for all-cause death by CSS was slightly larger comparing to SS but not significantly (AUC SS, 0.64; AUC CSS, 0.71; p = 0.23).

Conclusion: We concluded that both the SS and CSS were capable of risk stratification of clinical outcomes in all-comers population as well as in low and moderate risk Chinese patients undergoing PCI with CSS showing slightly better advantage.
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http://dx.doi.org/10.1186/s12872-021-02144-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265139PMC
July 2021

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Chin Med Sci J 2021 Jun;36(2):103-109

Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene () polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 μmol/L) (=0.006), while no effect of gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 μmol/L) (=0.491). Conclusion The C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.
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http://dx.doi.org/10.24920/003792DOI Listing
June 2021

The complete mitochondrial genome of (Hymenoptera: Crabronidae).

Mitochondrial DNA B Resour 2021 Jun 21;6(7):2044-2045. Epub 2021 Jun 21.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

The complete mitochondrial genome of the (Rossi, 1792) (Hymenoptera: Crabronidae) was obtained via next-generation sequencing. This mitochondrial genome is 16,188 bp in length with 37 classical eukaryotic mitochondrial genes and two A + T-rich region. All the 13 PCGs begin with typical ATN codons. Among them, eleven PCG genes terminate with TAA, two with T-. All of the 22 tRNA genes, ranging from 58 to 72 bp with typical cloverleaf structure except for trnS1, whose dihydrouridine (DHU) arm forms a simple loop. Phylogenetic analysis highly supported Crabronidae is the sister group of anthophila bees.
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http://dx.doi.org/10.1080/23802359.2021.1934146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218862PMC
June 2021

The complete mitochondrial genome of (Hymenoptera: Crabronidae).

Mitochondrial DNA B Resour 2021 Jun 14;6(7):1959-1960. Epub 2021 Jun 14.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

The complete mitochondrial genome of the (A. Costa, 1860) (Hymenoptera: Crabronidae) was obtained via next-generation sequencing. This mitochondrial genome is 16178 bp in length with 37 classical eukaryotic mitochondrial genes and an A + T-rich region. All the 13 PCGs begin with typical ATN codons. Among them, eleven PCG genes terminate with TAA, two with T--. All of the 22 tRNA genes, ranging from 58 to 72 bp with typical cloverleaf structure except for trnS1, whose dihydrouridine (DHU) arm forms a simple loop. Phylogenetic analysis highly supported Crabronidae shown as sister group of anthophila bees.
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http://dx.doi.org/10.1080/23802359.2021.1935344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204971PMC
June 2021

Leojaponin inhibits NLRP3 inflammasome activation through restoration of autophagy via upregulating RAPTOR phosphorylation.

J Ethnopharmacol 2021 Oct 9;278:114322. Epub 2021 Jun 9.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Provincial Center for Research & Development of Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, China. Electronic address:

Ethnopharmacological Relevance: Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis. This decoction consists of three Chinese herbal medicines, including Leonurus japonicus (L. japonicus), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases.

Aim Of The Study: To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus.

Materials And Methods: A series of compounds were isolated from L. japonicus. Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis. The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model.

Results: Here we show that Leojaponin, a diterpenoid compound from L. japonicus, suppressed lactate dehydrogenase and IL-1β release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo.

Conclusion: Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases.
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http://dx.doi.org/10.1016/j.jep.2021.114322DOI Listing
October 2021

Regulation of TWIK-related K channel 1 in the anterior hippocampus of patients with temporal lobe epilepsy with comorbid depression.

Epilepsy Behav 2021 08 8;121(Pt A):108045. Epub 2021 Jun 8.

Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Epilepsy, Beijing, China; Center of Epilepsy, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China. Electronic address:

Epilepsy with comorbid depression has recently attracted increasing attention. Temporal lobe epilepsy (TLE) may represent an increased risk of developing depression, especially if the seizures do not generalize. The two-pore domain potassium channel-TWIK-related K channel (TREK-1) plays important roles in both epilepsy and depression. However, the changes in its expression in patients with epilepsy with comorbid depression remain unclear. In the present study, we analyzed depressive symptoms using neuropsychiatric scales in forty-two patients with drug-resistant TLE, who also underwent EEG in waking and sleeping states, as well as 3.0 T brain MRI. We tested for TREK-1 positive neurons and microglial cells in the anterior hippocampi of patients with drug-resistant TLE with and without comorbid depression (n=5/group). Approximately 31% of patients with TLE had comorbid depression (13/42). Meanwhile, the patients who had hippocampal sclerosis had much higher scores on the depression rating scale. The results indicated the contribution of hippocampal sclerosis to the development of depression. Immunostaining of TREK-1 channels was observed in neurons and glia in the anterior hippocampus. Increased immunoreactivity of TREK-1 neurons was observed in the hippocampi of patients with TLE with comorbid depression compared with nondepressed patients with TLE. TREK-1 was expressed in almost all microglia. Curiously, more activated TREK-1-positive microglia were observed in patients with TLE with depression than in those without depression. The results suggested that a change in TREK-1 immunoreactivity was involved, at least partly, in the development of depression as a comorbidity of TLE. Imbalance of the TREK-1 channel may be a potential target for the treatment of patients with epilepsy with comorbid depression.
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http://dx.doi.org/10.1016/j.yebeh.2021.108045DOI Listing
August 2021

Tannic acid alleviates lipopolysaccharide‑induced H9C2 cell apoptosis by suppressing reactive oxygen species‑mediated endoplasmic reticulum stress.

Mol Med Rep 2021 Jul 3;24(1). Epub 2021 Jun 3.

Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

Sepsis‑induced myocardial dysfunction is one of the features of multiple organ dysfunction in sepsis, which is associated with extremely high mortality and is characterized by impaired myocardial compliance. To date, there are few effective treatment options available to cure sepsis. Tannic acid (TA) is reportedly protective during sepsis; however, the underlying mechanisms by which TA protects against septic heart injury remain elusive. The present study investigated the potential effects and underlying mechanisms of TA in alleviating lipopolysaccharide (LPS)‑induced H9C2 cardiomyocyte cell apoptosis. H9C2 cells were treated with LPS (15 g/ml), TA (10 M) and TA + LPS; control cells were treated with medium only. Apoptosis was measured using flow cytometry, reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Additionally, the levels of cellular reactive oxygen species (ROS), malondialdehyde and nicotinamide adenine dinucleotide phosphate were evaluated. Western blotting and RT‑qPCR were also employed to detect the expression levels of endoplasmic reticulum (ER) stress‑associated functional proteins. The present findings demonstrated that TA reduced the degree of LPS‑induced H9C2 cell injury, including inhibition of ROS production and ER stress (ERS)‑associated apoptosis. ERS‑associated functional proteins, including activating transcription factor 6, protein kinase‑like ER kinase, inositol‑requiring enzyme 1, spliced X box‑binding protein 1 and C/EBP‑homologous protein were suppressed in response to TA treatment. Furthermore, the expression levels of ERS‑associated apoptotic proteins, including c‑Jun N‑terminal kinase, Bax, cytochrome c, caspase‑3, caspase‑12 and caspase‑9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS‑induced H9C2 cells were partially inhibited following treatment with the ROS inhibitor N‑acetylcysteine, which demonstrated that ROS mediated ERS‑associated apoptosis and TA was able to decrease ROS‑mediated ERS‑associated apoptosis. Collectively, the present findings demonstrated that the protective effects of TA against LPS‑induced H9C2 cell apoptosis may be associated with the amelioration of ROS‑mediated ERS. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury.
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http://dx.doi.org/10.3892/mmr.2021.12174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170226PMC
July 2021

[Screening results and genetic features of glucose-6-phosphate dehydrogenase deficiency in 54 025 preterm infants in Chengdu, China].

Zhongguo Dang Dai Er Ke Za Zhi 2021 May;23(5):482-487

Department of Neonatal Screening, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611731, China.

Objective: To analyze the screening results of glucose-6-phosphate dehydrogenase (G6PD) deficiency and gene mutation distribution of G6PD deficiency in preterm infants in Chengdu, China, in order to provide a basis for the improvement of G6PD screening process in preterm infants.

Methods: Fluorescent spot test for G6PD deficiency using dried blood spots was used for G6PD screening of 54 025 preterm infants born from January 1, 2015 to December 31, 2019 in Chengdu, and G6PD enzymology and gene detection were used for the diagnosis of 213 infants with positive screening results.

Results: Among the 54 025 preterm infants, 192 were diagnosed with G6PD deficiency, with an incidence rate of 3.55‰. The incidence rate of G6PD deficiency in preterm infants was higher than that in full-term infants in the same period of time and tended to increase year by year. Birth in summer, gestational age <32 weeks, and birth weight <2 500 g were influencing factors for the increase in false positive rate of screening ( < 0.05). The diagnostic accordance rate of genetic tests was significantly higher than that of enzyme activity assay in female infants ( < 0.05). Nine gene mutations were detected in Chengdu, without compound heterozygous mutation. Homozygous mutation was not detected in female infants. In the 80 infants with gene mutations, the top three gene mutations were c.1388G>A in 26 infants (32%), c.1376G>T in 21 infants (26%), and c.1024C>T in 13 infants (16%), accounting for 75%. There was a significant difference in pathogenicity grading among the three gene mutations ( < 0.001). The pairwise comparison showed that c.1024C>T had a significantly lower pathogenicity grade than c.1376G>T and c.1388G>A ( < 0.0167), suggesting that c.1376G>T and c.1388G>A had greater influence on enzyme activity than c.1024C>T.

Conclusions: Screening for G6PD deficiency in preterm infants should be taken seriously. It is recommended to apply cold-chain transportation of samples in summer to reduce the false positive rate of primary screening for G6PD deficiency. Genetic tests should be promoted in girls with positive screening results to improve the detection rate of G6PD deficiency in preterm female infants. There are various types of gene mutations in preterm infants with G6PD deficiency in Chengdu, and infants with c.1024C>T mutation tend to have mild conditions.
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May 2021

Prophylactic administration of fingolimod (FTY720) ameliorated experimental autoimmune myasthenia gravis by reducing the number of dendritic cells, follicular T helper cells and antibody-secreting cells.

Int Immunopharmacol 2021 Jul 27;96:107511. Epub 2021 Apr 27.

Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, China; Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, China; Shandong Institute of Neuroimmunology, China. Electronic address:

Fingolimod (FTY720), a sphingosine 1-phosphate (S1P) receptor antagonist, possesses potent immunomodulatory activity via lymphocyte homing. The effects of FTY720 have been widely studied in various T-cell-mediated autoimmune diseases, while the immunomodulatory effects on experimental autoimmune myasthenia gravis (EAMG), a typical disease model for antibody-mediated autoimmunity, remain elusive. In the present study, FTY720 was administered to EAMG rats as prophylaxis. The clinical scores were recorded every other day, and serum antibodies at different time points were measured by enzyme-linked immunosorbent assay (ELISA). The immune cell subsets in the spleen, bone marrow, circulation, and thymus were determined by flow cytometry. The prophylactic administration alleviated EAMG symptoms by reducing the level of serum antibodies IgG and its isotype IgG2b on days 30 and 46 post immunization, as well as IgG and Ig kappa antibody-secreting cells in the spleen and bone marrow. The mitigated humoral immune response can be attributed to the decreased dendritic cells, follicular T help cells (Tfh) and Tfh subsets (Tfh1, Tfh2, and Tfh17), and T helper cell subsets (Th1, Th2, and Th17) in the spleen. The promotion of lymphocyte homing and inhibition of thymocyte egress contribute to the effects of FTY720 on these effector T cell subsets. Overall, the prophylactic administration of FTY720 ameliorated EAMG partially by regulating humoral immune response,suggesting that FTY720 could be part of a pharmacological strategy for managing myasthenia gravis.
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http://dx.doi.org/10.1016/j.intimp.2021.107511DOI Listing
July 2021

A new surgical technique for post-myocardial infarction ventricular septal rupture with hemodynamic instability.

Chin Med J (Engl) 2021 Apr 7;134(8):981-983. Epub 2021 Apr 7.

Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

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http://dx.doi.org/10.1097/CM9.0000000000001442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078452PMC
April 2021

A three-year clinical investigation of a Chinese child with craniometaphyseal dysplasia caused by a mutated gene.

World J Clin Cases 2021 Mar;9(8):1853-1862

Shanghai AhCare Consulting, Shanghai 20120, China.

Background: Craniometaphyseal dysplasia (CMD) is a rare genetic disorder. Autosomal dominant CMD (AD-CMD) is caused by mutations in the gene. Affected individuals typically have distinctive facial features including progressive thickening of the craniofacial bones. Treatment for AD-CMD primarily consists of surgical intervention to release compression of the cranial nerves and the brain stem/spinal cord. To alleviate progression of the clinical course and improve the quality of life in children waiting to undergo the necessary surgery, we investigated clinical changes in a diagnosed patient with AD-CMD over three years.

Case Summary: A 17-mo-old boy presented with progressive nasal obstruction, snoring and hearing loss symptoms. Physical examination showed enlargement of the head circumference and clinical features such as wide nasal bridge, paranasal bossing, widely spaced eyes with an increased bizygomatic width, and a prominent mandible. The patient underwent otolaryngological examination, endoscopy, hearing test, laboratory examination of phosphorus and bone metabolism, cranial and femoral computed tomography, X-ray and next-generation sequencing. The patient was diagnosed with AD-CMD due to p.Phe377 deletion (c.1129_1131del) on exon 9 of the gene. After adherence to a prescribed low-calcium diet, the boy's alkaline phosphatase (ALP) levels continuously decreased to within the normal range. However, after 14 mo of dietary intervention, his parents altered his diet to an intermittent low-calcium diet to include milk and eggs. The patient's ALP was slightly higher than normal after the dietary change but remained close to the normal range. His serum osteocalcin changed to within normal levels after dietary regulation for 33 mo. His serum combined beta C-terminal telopeptide of type I collagen also continuously decreased after the nutritional intervention, although still slightly higher than normal levels. Despite fluctuating blood test results, the boy's nasal symptoms were markedly relieved and steadily improved after dietary intervention. No significant changes were found in the craniofacial bones by cranial radiography. Close monitoring of clinical features is still ongoing. Calcitriol treatment is currently under consideration and a surgical procedure is planned as necessary in the future.

Conclusion: We herein report the first Chinese case of AD-CMD with heterozygous mutation of p.Phe377 deletion (c.1129_1131del) on the gene. Biochemical alterations were significantly improved after dietary intervention indicating that a low-calcium diet may be applied in pediatric AD-CMD patients with mutations to help alleviate phenotypic manifestations and improve the quality of life before surgical intervention. Further large scale studies are needed to replicate these findings and to establish the appropriate timing for nutritional and surgical interventions.
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http://dx.doi.org/10.12998/wjcc.v9.i8.1853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953411PMC
March 2021

Synthesis of nigranoic acid and manwuweizic acid derivatives as HDAC inhibitors and anti-inflammatory agents.

Bioorg Chem 2021 Apr 16;109:104728. Epub 2021 Feb 16.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Research & Development Center for Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address:

As a successful anti-tumor drug target, the family of histone deacetylases (HDACs) is also a critical player in immune response, making the research of anti-inflammatory HDAC inhibitors an attractive new focus. In this report, triterpenoids nigranoic acid (NA) and manwuweizic acid (MA) were identified as HDAC inhibitors through docking-based virtual screening and enzymatic activity assay. A series of derivatives of NA and MA were synthesized and assessed for their biological effects. As a result, hydroxamic acid derivatives of NA and MA showed moderately increased activity for HDAC1/2/4/6 inhibition (the lowest IC against HDAC1 is 1.14 μM), with no activity against HDAC8. In J774A.1 macrophage, compound 1-3, 13 and 17-19 demonstrated inhibitory activity against lactate dehydrogenase (LDH) and IL-1β production, without affecting cell viability. Compound 19 increased the histone acetylation level in J774A.1 cells, as well as inhibited IL-1β maturation and caspase-1 cleavage. These results indicated that compound 19 blocks the activation of NLRP3 inflammasome, probably related to HDAC inhibition. This work provided a natural scaffold for developing low-cytotoxic and anti-inflammatory HDAC inhibitors, as well as a class of tool molecules for studying the relationship between HDACs and NLRP3 activation.
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http://dx.doi.org/10.1016/j.bioorg.2021.104728DOI Listing
April 2021

Effects of D-pinitol on myocardial apoptosis and fibrosis in streptozocin-induced aging-accelerated mice.

J Food Biochem 2021 04 18;45(4):e13669. Epub 2021 Feb 18.

Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China.

Diabetic cardiomyopathy (DCM) causes heart failure and increases the mortality in diabetic patients. Myocardial apoptosis and fibrosis are the main features of DCM and aging. The aim is to study the underlying mechanism of D-pinitol (DP) on myocardial apoptosis and fibrosis in an elderly diabetic mouse model. The diabetic model was established by SAMP-8 mice that were injected with streptozotocin daily for five consecutive days. The mice were administrated of DP (150 mg kg  day ) by gavage for 10 weeks. The common metabolic disorder indices, cardiac dysfunction, oxidative stress, myocardial apoptosis and fibrosis, and PI3K/Akt/mTOR pathway were investigated. Our findings suggested that DP has a protective effect on DCM, which may be related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP may be a novel clinical application in fighting against DCM. PRACTICAL APPLICATIONS: D-pinitol (DP) was found in large quantities in soybean and legume foods. DP has a variety of functions, including hypoglycemic, anti-oxidation, anti-inflammatory, cardioprotective, and anti-tumor activity. We used the streptozotocin-induced SAMP8 mice as the diabetic model and treated with DP. We found that DP can improve cardiac dysfunction and inhibits the oxidative stress, myocardial apoptosis and fibrosis. DP has a significant effect on diabetic cardiomyopathy (DCM). The molecular mechanisms are related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP can prevent and/or delay the onset of DCM.
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http://dx.doi.org/10.1111/jfbc.13669DOI Listing
April 2021

Proangiogenic Peptide Nanofiber Hydrogels for Wound Healing.

ACS Biomater Sci Eng 2021 03 29;7(3):1100-1110. Epub 2021 Jan 29.

Department of Biomedical Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, P. R. China.

Rapid vascularization is vital for dermal regeneration, nutrient and nutrition transfer, metabolic waste removal, and prevention of infection. This study reports on a series of proangiogenic peptides designed to undergo self-assembly and promote angiogenesis and hence skin regeneration. The proangiogenic peptides comprised an angiogenic peptide segment, GEETEVTVEGLEPG, and a β-sheet structural peptide sequence. These peptides dissolved easily in ultrapure water and rapidly self-assembled into hydrogels in a pH-dependent manner, creating three-dimensional fibril network structures and nanofibers as revealed by a scanning microscope and a transmission electron microscope. experiments showed that the peptide hydrogels favored adhesion and proliferation of mouse fibroblasts (L929) and human umbilical vein endothelial cells (HUVECs). In particular, many connected tubes were formed in the HUVECs after 8 h of culture on the peptide hydrogels. experiments demonstrated that new blood vessels grew into the proangiogenic peptide hydrogels within 2 weeks after subcutaneous implantation in mice. Moreover, the proangiogenic-combined hydrogels exhibited faster repair cycles and better healing of skin defects. Collectively, the results indicate that the proangiogenic peptide hydrogels are a promising therapeutic option for skin regeneration.
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http://dx.doi.org/10.1021/acsbiomaterials.0c01264DOI Listing
March 2021

Toonaones A-I, limonoids with NLRP3 inflammasome inhibitory activity from Toona ciliata M. Roem.

Phytochemistry 2021 Apr 14;184:112661. Epub 2021 Jan 14.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan, 650091, China. Electronic address:

Nine undescribed limonoids, 18(13 → 14)-abeo-15β,21-dihydroxy-24,25,26,27-tetranor-3,7-dioxoapotirucalla-1,9(11),13(17),20(22)-tetraen-23,21-olide (Toonaone A), 21-hydroxy-24,25,26,27-tetranor-3,7,15-trioxoapotirucalla-1,9(11),20(22)-trien-23,21-olide (Toonaone B), 7α,21-dihydroxy-12α-isobutyryl-24,25,26,27-tetranor-3,15-dioxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone C), 7,8-seco-7-methyl ester-11β-acetoxy-14β,15β-epoxy-21-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone D), 7,8-seco-7-methyl ester-11β-acetoxy-14β,15β-epoxy-23-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-21,23-olide (Toonaone E), 7,8-seco-7-methyl ester-11β-acetoxy-14β,15β-epoxy-6β,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone F), 7,8-seco-7-methyl ester-14β,15β-epoxy-8α,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone G), 7,8-seco-7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone H), 7,8-seco-7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-21,23-diimide (Toonaone I), and five known analogues were isolated from the twigs of Toona ciliata M. Roem. (Meliaceae). Toonaone A possesses the first rare 18(13 → 14)-abeo-limonoid skeleton reported from the genus Toona. Their structures were elucidated using spectroscopic data analyses and quantum chemistry calculations. Biological evaluation showed that toonaone C, toonaone D, toonaone G, toonaciliatavarin F, and toonaciliatavarin G exhibited significant anti-NLRP3 inflammasome activity with IC values ranging from 3.74 to 18.7 μM. GMDMD, IL-1β, and caspase-1 analyses suggested that toonaone D inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis.
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http://dx.doi.org/10.1016/j.phytochem.2021.112661DOI Listing
April 2021

Precise diagnosis of three top cancers using dbGaP data.

Sci Rep 2021 01 12;11(1):823. Epub 2021 Jan 12.

Huaiyin Institute of Technology, Huaian, 223003, China.

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240-370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.
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http://dx.doi.org/10.1038/s41598-020-80832-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804208PMC
January 2021

Dioscin inhibits human endometrial carcinoma proliferation via G0/G1 cell cycle arrest and mitochondrial-dependent signaling pathway.

Food Chem Toxicol 2021 Feb 24;148:111941. Epub 2020 Dec 24.

School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address:

The present study emphasized on the anti-cancerous effects of dioscin and its underlying molecular mechanism in human endometrial cancer Ishikawa cells. Dioscin significantly suppressed the proliferation of Ishikawa cells at IC of 2.37 μM. Besides, dioscin could inhibit the proliferation of Ishikawa cells by blocking the G0/G1 cell cycle through up-regulation of p16, p21, and p27 and down-regulation of cycle-cellular protein (Cyclin A/D/E) and cyclin-dependent kinase (CDK2/4/6). Also, it promoted apoptosis through the mitochondrial pathway, including the regulation of Bcl family proteins, the increase of ROS levels, the activation of caspases (Caspase 9/3), and the decrease of mitochondrial membrane permeability. Whereas dioscin also effectively activated the marker genes and proteins (Fas, TNF-R1, and Caspase 8) related to the death receptor-mediated pathway which confirmed the involvement of both the pathways for dioscin-induced apoptosis. The current results demonstrated that dioscin possessed potential health benefits with respect to endometrial cancer prevention and treatment.
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http://dx.doi.org/10.1016/j.fct.2020.111941DOI Listing
February 2021

Endothelium-specific endothelin-1 expression promotes pro-inflammatory macrophage activation by regulating miR-33/NR4A axis.

Exp Cell Res 2021 02 16;399(1):112443. Epub 2020 Dec 16.

Cardiac Center & Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

The hallmark of atherogenesis is characterized as endothelial dysfunction and subsequent macrophage activation. Although our previous study has demonstrated that endothelin-1 (ET-1) plays an important role in atherogenesis, the underlying mechanism remains deeply investigation. Enhanced atherosclerotic plaques were observed in endothelium-specific ET-1 overexpression ApoE mice (eET-1/ApoE) concomitant with increased secretion of pro-inflammatory adhesion molecules and cytokines. The conditional media used for culturing human umbilical vein endothelial cells (HUVECs) with AdET-1 infection and subjected to OX-LDL stimulation, was collected and utilized for bone marrow-derived macrophages (BMDMs) culturing. RT-PCR analysis showed increased genes expression related to classical M1 macrophages but decreased alternative activated M2 macrophages genes expression in macrophage culturing with the conditional media. Furthermore, consistent regulations of macrophage polarization were observed using isolated exosomes from the conditional media. More importantly, we noticed that miR-33 was enriched in the exosomes derived by HUVECs with AdET-1 infection, while bioinformatics analysis further indicated that miR-33 directly targeted NR4A and miR-33/NR4A axis was required for the effect of endothelial-specific ET-1 overexpression on pro-inflammatory macrophage activation. By contrast, such effects could be reversed by ET-1 knockdown. Taken together, our study indicated that the exosomes derived by HUVECs with AdET-1 infection can transfer miR-33 to macrophages and subsequently promote pro-inflammatory macrophage activation by directly targeting to NR4A. These evidences clearly revealed that miR-33/NR4A axis was the important mechanism underlying the effect of ET-1 on macrophage activation and indicated that ET-1 may act as a promising target for atherosclerosis management.
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http://dx.doi.org/10.1016/j.yexcr.2020.112443DOI Listing
February 2021

Recent advances in network-based methods for disease gene prediction.

Brief Bioinform 2021 Jul;22(4)

Department head and principal scientist at I2R, A*STAR, Singapore.

Disease-gene association through genome-wide association study (GWAS) is an arduous task for researchers. Investigating single nucleotide polymorphisms that correlate with specific diseases needs statistical analysis of associations. Considering the huge number of possible mutations, in addition to its high cost, another important drawback of GWAS analysis is the large number of false positives. Thus, researchers search for more evidence to cross-check their results through different sources. To provide the researchers with alternative and complementary low-cost disease-gene association evidence, computational approaches come into play. Since molecular networks are able to capture complex interplay among molecules in diseases, they become one of the most extensively used data for disease-gene association prediction. In this survey, we aim to provide a comprehensive and up-to-date review of network-based methods for disease gene prediction. We also conduct an empirical analysis on 14 state-of-the-art methods. To summarize, we first elucidate the task definition for disease gene prediction. Secondly, we categorize existing network-based efforts into network diffusion methods, traditional machine learning methods with handcrafted graph features and graph representation learning methods. Thirdly, an empirical analysis is conducted to evaluate the performance of the selected methods across seven diseases. We also provide distinguishing findings about the discussed methods based on our empirical analysis. Finally, we highlight potential research directions for future studies on disease gene prediction.
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http://dx.doi.org/10.1093/bib/bbaa303DOI Listing
July 2021

A Naringin- and Icariin-Contained Herbal Formula, Gushukang, Ameliorated Aged Osteoporosis of Aged Mice with High Calcium Intake.

Am J Chin Med 2020 ;48(7):1671-1691

Spine Disease Research Institute, Longhua Hospital, Shanghai University of Traditional, Chinese Medicine, Shanghai 200032, P. R. China.

Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis and showed osteoprotective effect in ovariectomized rodent animals and regulatory action on calcium transporters. This study aimed to determine if GSK could ameliorate aged osteoporosis by modulating serum level of calciotropic hormones and improving calcium balance. 18-month-old male mice were orally administered with either GSK (0.38[Formula: see text]g/kg body weight) or calcitriol (1[Formula: see text][Formula: see text]g/kg body weight) combined with high calcium diet (HCD, 1.2% Ca) for 60 days. The aged mice fed with normal calcium diet (NCD, 0.6% Ca) were a negative control. Trabecular bone and cortical bone properties as well as calcium balance were determined. Treatment with GSK significantly increased 25(OH)D and 1,25-(OH)D levels in serum, moreover, it markedly attenuated trabecular bone micro-architectural deteriorations and elevated trabecular bone mass as well as strengthened cortical bone mechanical properties shown by the increase in maximal bending load and elastic modulus. Calcium balance, including urinary Ca excretion, fecal Ca level and net calcium retention, was remarkably improved by GSK, which up-regulated TRPV6 expression in duodenum and TRPV5 expression in kidney and down-regulated claudin-14 expression in duodenum and kidney. Additionally, 1-OHase and 24-OHase expression was significantly decreased ( NCD group) and increased ( HCD group), respectively, in kidney of GSK- and calcitriol-treated mice. Taken together, this study demonstrated the ameliorative effects of Gushukang on aged osteoporosis by effectively stimulating vitamin D production and improving calcium balance of aged mice with high dietary calcium supplement.
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http://dx.doi.org/10.1142/S0192415X20500834DOI Listing
February 2021

MRI-Based radiomics nomogram for differentiation of benign and malignant lesions of the parotid gland.

Eur Radiol 2021 Jun 19;31(6):4042-4052. Epub 2020 Nov 19.

Department of Radiology, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, 266000, China.

Objectives: Preoperative differentiation between benign parotid gland tumors (BPGT) and malignant parotid gland tumors (MPGT) is important for treatment decisions. The purpose of this study was to develop and validate an MRI-based radiomics nomogram for the preoperative differentiation of BPGT from MPGT.

Methods: A total of 115 patients (80 in training set and 35 in external validation set) with BPGT (n = 60) or MPGT (n = 55) were enrolled. Radiomics features were extracted from T1-weighted and fat-saturated T2-weighted images. A radiomics signature model and a radiomics score (Rad-score) were constructed and calculated. A clinical-factors model was built based on demographics and MRI findings. A radiomics nomogram model combining the Rad-score and independent clinical factors was constructed using multivariate logistic regression analysis. The diagnostic performance of the three models was evaluated and validated using ROC curves on the training and validation datasets.

Results: Seventeen features from MR images were used to build the radiomics signature. The radiomics nomogram incorporating the clinical factors and radiomics signature had an AUC value of 0.952 in the training set and 0.938 in the validation set. Decision curve analysis showed that the nomogram outperformed the clinical-factors model in terms of clinical usefulness.

Conclusions: The above-described radiomics nomogram performed well for differentiating BPGT from MPGT, and may help in the clinical decision-making process.

Key Points: • Differential diagnosis between BPGT and MPGT is rather difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, clinical data, and MRI features facilitates differentiation of BPGT from MPGT with improved diagnostic efficacy.
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http://dx.doi.org/10.1007/s00330-020-07483-4DOI Listing
June 2021

Rubellawus A-D, Four New Diterpenoids Isolated from Callicarpa rubella and Their Anti-NLRP3 Inflammasome Effects.

Chem Biodivers 2020 Dec 26;17(12):e2000798. Epub 2020 Nov 26.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Research and Development Center for Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, P. R. China.

Four new diterpenoids, rubellawus A-D (1-4), along with three known compounds, were isolated and identified from the flowers of Callicarpa rubella. Their structures were elucidated by various spectroscopic analysis. All the compounds were screened for their anti-inflammatory activity and 14α-hydroxyisopimaric acid and isopimaric acid showed significant NLRP3 inflammasome inhibitory activity with IC values of 7.02 and 3.99 μM.
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http://dx.doi.org/10.1002/cbdv.202000798DOI Listing
December 2020

Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis.

World J Gastrointest Oncol 2020 Oct;12(10):1195-1208

Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis.

Aim: To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis.

Methods:

T:

Results: The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits.

Conclusion: This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.
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http://dx.doi.org/10.4251/wjgo.v12.i10.1195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579736PMC
October 2020

Chronic Application of Low-Dose Aspirin Affects Multiple Parameters of Three Blood Cellular Types and Antithrombin Activity: A 1:1:1 Propensity Score Matching Analysis.

J Cardiovasc Pharmacol 2021 01;77(1):115-121

Department of Geriatric Cardiology, The Second Medical Center, The National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China; and.

Abstract: The mechanisms of aspirin antithrombotic actions have not been fully elucidated. We re-analyzed the data from the project Aspirin Resistance in Patients with Ischemic Atherothrombotic Diseases from April 2008 to June 2010. A total of 530 subjects were classified into 3 groups, including 40 patients without aspirin use, 24 patients taking 25-50 mg/d aspirin, and 466 patients taking 75-100 mg/d aspirin over 1 month. By 1:1:1 propensity score matching adjusting 15 primary clinical covariates, 51 patients (n = 17 per group) comprised the final sample. Hemostasis-related parameters and high platelet reactivity as measured by arachidonic acid-induced and adenosine diphosphate-induced light transmission aggregometry were compared in the 3 groups. A dose-dependent relationship was observed between aspirin and decreased high platelet reactivity incidence (PAA < 0.001, PADP < 0.01, respectively), decreased monocyte ratio (P = 0.052), increased antithrombin activity (P < 0.001), and increased platelet distribution width (P < 0.05). Aspirin at 25-50 mg/d is related to the lowest red blood cell (RBC) count, whereas 75-100 mg/d aspirin showed the highest RBC count among the 3 groups (4.52 ± 0.35 × 1012/L vs. 4.35 ± 0.57 × 1012/L vs. 4.80 ± 0.59 × 1012/L, P = 0.046). Our finding demonstrated that aspirin exerts its antithrombotic effects at least by antiplatelet function, enhancing antithrombin activity and suppressing monocytes in vivo. In addition, 3 blood cell types, namely RBCs, monocytes, and platelets, are involved in the aspirin antithrombotic mechanism. The cellular response to aspirin partially enhances the antithrombotic effects while partially inhibiting the effects.
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http://dx.doi.org/10.1097/FJC.0000000000000939DOI Listing
January 2021

Toonaolides A-X, limonoids from Toona ciliata: Isolation, structural elucidation, and bioactivity against NLRP3 inflammasome.

Bioorg Chem 2020 12 10;105:104363. Epub 2020 Oct 10.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China. Electronic address:

Twenty-four new limonoids, toonaolides A-X (1-24), characterized with an α,β-unsaturated-γ-lactone A-ring were isolated from the twigs of Toona ciliata. Their structures and absolute configurations were elucidated by spectroscopic data, X-ray diffraction crystallography, and quantum chemistry calculations. Most of the isolated compounds (except 9, 18, and 24 which possessed the maleimide ring) featured the rare 21-hydroxybutenolide or 23-hydroxybutenolide moieties. In particular, compound 1 has an unprecedented limonoid architecture with 6/6 cis-fused A/B ring system and 2 has an unusual tetrahydrofuran ring B skeleton, featuring a 7/5/6/5 ring system. The biological evaluation showed that compounds 9, 11, 12, 14, and 18 exhibited significantly anti-NLRP3 inflammasome activity with IC values ranging from 3.2 to 9.7 μM. Analysis of IL-1β and caspase-1 expression revealed that compounds 11 and 12 are selective inhibitors of NLRP3 inflammasome, which could ameliorate cell pyroptosis by blocking NLRP3 inflammasome activation.
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http://dx.doi.org/10.1016/j.bioorg.2020.104363DOI Listing
December 2020

Euphopias A-C: Three Rearranged Jatrophane Diterpenoids with Tricyclo[8.3.0.0]tridecane and Tetracyclo[11.3.0.0.0]hexadecane Cores from .

Org Lett 2020 10 29;22(20):7820-7824. Epub 2020 Sep 29.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Research & Development Center for Natural Products; School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. China.

Euphopias A-C (-), three rearranged jatrophane-type diterpenoids with tricyclo[8.3.0.0]tridecane ( and ) and tetracyclo[11.3.0.0.0]hexadecane () cores, were isolated from . Comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray diffractions were used to identify their structures. Compounds - could significantly inhibit NLRP3 inflammasome activation and block NLRP3 inflammasome-induced pyroptosis. Additionally, a mechanistic study revealed that could ameliorate mitochondria damage, thereby interrupting NLRP3 inflammasome activation.
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http://dx.doi.org/10.1021/acs.orglett.0c02676DOI Listing
October 2020

Structurally Diverse Labdane Diterpenoids from and Their Anti-inflammatory Properties in LPS-Induced RAW264.7 Cells.

J Nat Prod 2020 09 16;83(9):2545-2558. Epub 2020 Sep 16.

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Research & Development Center for Natural Products, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China.

A phytochemical study on the aerial parts of led to the isolation and identification of 38 labdane diterpenoids, including 18 new (, , , , -, , -, , ) and 20 known (-, -, , , -, , ) analogues. Their structures were elucidated based on physical data analysis, including 1D and 2D NMR, HRMS, UV, IR, and X-ray diffraction. The structure of the known compound was confirmed by single-crystal X-ray diffraction data. These compounds can be divided into furanolabdane (-), tetrahydrofuranolabdane (-), lactonelabdane (-), labdane (-), and -labdane (-) type diterpenoids. All compounds were screened by lipopolysaccharide (LPS)-induced nitric acid (NO) production in RAW264.7 cells to evaluate anti-inflammatory effects. Compounds , , -, -, -, and inhibited NO production with IC values lower than 50 μM, with compound being the most active, with an IC value of 3.9 ± 1.7 μM. Further studies show that compound inhibits pro-inflammatory cytokine production and IKK α/β phosphorylation and restores the IκB expression levels in the NF-κB signaling pathway.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00597DOI Listing
September 2020